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程序性死亡受体1(PD-1)单抗联合索拉非尼或仑伐替尼治疗肝功能Child-Pugh B级不可切除肝癌患者的效果分析

孙巍 丁晓燕 陈京龙

引用本文:
Citation:

程序性死亡受体1(PD-1)单抗联合索拉非尼或仑伐替尼治疗肝功能Child-Pugh B级不可切除肝癌患者的效果分析

DOI: 10.12449/JCH240517
基金项目: 

首都卫生发展科研专项 (2022-2-2175)

医学伦理声明本研究于2021年9月1日经由首都医科大学附属北京地坛医院伦理委员会批准,批号:JDLKZ-2021-041-01。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:孙巍负责设计论文框架,起草论文,研究过程的实施;丁晓燕负责数据收集,统计学分析,绘制图表;陈京龙负责论文修改,负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    陈京龙, dingxiaoyan198111@163.com (ORCID: 0000-0003-1640-7115)

Efficacy and safety of anti-PD-1 monoclonal antibody combined with sorafenib or lenvatinib in treatment of patients with Child-Pugh class B unresectable hepatocellular carcinoma

Research funding: 

Capital Health Development Research Project (2022-2-2175)

More Information
  • 摘要:   目的  回顾性分析酪氨酸激酶抑制剂联合免疫检查点抑制剂在肝功能Child-Pugh B级不可切除肝癌(uHCC)患者中的疗效和安全性。  方法  纳入2020年12月31日—2023年3月30日首都医科大学附属北京地坛医院收治的肝功能Child-Pugh B级的uHCC患者96例,接受仑伐替尼联合程序性细胞死亡-1(PD-1)抑制剂治疗者为L组(63例),接受索拉非尼联合PD-1抑制剂治疗者为S组(33例)。主要终点为客观缓解率(ORR),次要终点包括疾病进展时间(TTP)、总生存期(OS)、毒性、停药率和剂量调整率。符合正态分布的计量资料2组间比较采用成组t检验;非正态分布2组间比较采用Mann-Whitney U检验。计数资料2组间比较采用χ2检验。绘制生存曲线,运用Kaplan-Meier法计算2组患者的生存率,并利用Log-rank检验比较2组差异。通过Cox回归模型计算风险比(HR)和95%置信区间(95%CI),实现预后影响因素的多因素分析。  结果  96例uHCC患者中,Child-Pugh B级(7分)55例(57.3%),B级(8~9分)41例(42.7%)。L组患者的ORR显著高于S组(46.0% vs 15.2%,P=0.003)。L组和S组中位TTP(6.6个月 vs 3.5个月,P=0.48)或OS(13.8个月 vs 13.2个月,P=0.95)差异无统计学意义。Child-Pugh B级(7分)患者与Child-Pugh B级(8~9分)患者的中位TTP差异无统计学意义(6.6个月 vs 4.8个月,P=0.35),OS具有统计学意义(14.5个月 vs 8.8个月,P=0.045)。多因素分析显示,ORR是TTP(HR=0.18,95%CI:0.09~0.36,P<0.001)和OS(HR=0.20,95%CI:0.09~0.43,P<0.001)的保护因素。L组和S组总体不良反应(98.4% vs 97.0%)和≥3级不良反应的发生率(68.3% vs 63.6%)比较,差异均无统计学意义。L组和S组在剂量调整率(84.8% vs 70.2%)或停药率(56.1% vs 72.7%)方面无显著差异。  结论  与索拉非尼联合PD-1抑制剂方案相比,仑伐替尼联合PD-1抑制剂方案改善了Child-Pugh B级uHCC患者的ORR,但两组总体预后相似,总体安全性相当。

     

  • 图  1  L组和S组患者的TTP和OS比较

    Figure  1.  Comparison of TTP and OS between the two groups of patients

    图  2  Child-Pugh B级(7分)患者与Child-Pugh B级(8~9分)患者的TTP和OS比较

    Figure  2.  Comparison of TTP and OS in the patients with Child-Pugh class B(7 points)and Child-Pugh class B(8—9 points)

    表  1  2组患者一般资料及肿瘤情况比较

    Table  1.   Baseline patient demographic and disease characteristics

    指标 合计 L组(n=63) S组(n=33) 统计值 P
    年龄(岁) 62(29~82) 62(30~82) 64(29~74) Z=-0.10 0.92
    男/女(例) 84/12 55/8 29/4 χ2=0.01 0.94
    ECOG评分[例(%)] χ2=0.86 0.40
    0分 49(51.0) 30(47.6) 19(57.6)
    1分 47(49.0) 33(52.4) 14(42.4)
    嗜肝病毒感染[例(%)] χ2=3.13 0.21
    HBV 86(89.6) 54(85.7) 32(97.0)
    HCV 7(7.3) 6(9.5) 1(3.0)
    非HBV或HCV 3(3.1) 3(4.8) 0(0.0)
    Child-Pugh评分 χ2=0.00 >0.05
    B级(7分) 55(57.3) 36(57.1) 19(57.6)
    B级(8~9分) 41(42.7) 27(42.9) 14(42.4)
    肝外转移[例(%)] χ2=0.58 0.52
    40(41.7) 28(44.4) 12(36.4)
    56(58.3) 35(55.6) 21(63.6)
    合并门静脉癌栓[例(%)] χ2=0.32 0.66
    59(61.5) 40(63.5) 19(57.6)
    37(38.5) 23(36.5) 14(42.4)
    靶病灶直径(cm) 8.9(8.8~10.8) 9.0(7.5~11.2) 7.9(6.2~10.2) Z=-1.61 0.07
    肝内肿瘤个数[例(%)] χ2=0.56 0.50
    1~3个 63(65.6) 43(68.3) 20(60.6)
    ≥4个 33(34.4) 20(31.7) 13(39.4)
    AFP[例(%)] χ2=0.83 0.39
    ≥400 ng/mL 55(57.3) 34(54.0) 21(63.6)
    <400 ng/mL 41(42.7) 29(46.0) 12(36.4)
    下载: 导出CSV

    表  2  依据mRECIST标准评估的肿瘤反应率

    Table  2.   Response rates according to the mRECIST

    疗效 L组(n=63) S组(n=33) χ2 P
    CR[例(%)] 0(0.0) 0(0.0)
    PR[例(%)] 29(46.0) 5(15.2) 9.03 0.003
    SD[例(%)] 25(39.7) 19(57.6) 2.79 0.134
    PD[例(%)] 9(14.3) 9(27.3) 2.40 0.172
    DCR(%) 85.7 72.7 2.40 0.171
    下载: 导出CSV

    表  3  依据iRECIST标准评估的肿瘤反应率

    Table  3.   Response rates according to the iRECIST

    疗效 L组(n=63) S组(n=33) χ2 P
    iCR[例(%)] 0(0.0) 0(0.0)
    iPR[例(%)] 29(46.0) 5(15.2) 9.03 0.003
    iSD[例(%)] 25(39.7) 19(57.6) 2.79 0.134
    iUPD[例(%)] 9(14.3) 9(27.3) 2.40 0.172
    iCPD[例(%)] 9(14.3) 9(27.3) 2.40 0.172
    DCR(%) 85.7 72.7 2.40 0.171
    下载: 导出CSV

    表  4  TTP的多变量Cox比例风险模型分析

    Table  4.   Multivariable Cox proportional hazards model for time to progression

    变量 HR 95%CI P
    ORR(是=0/否=1) 0.18 0.09~0.36 <0.001
    肿瘤最大径(≤7 cm=0/>7 cm=1) 0.55 0.29~1.06 0.074
    AFP(≥400 ng/mL=0/<400 ng/mL=1) 1.00 0.58~1.72 >0.05
    肝外转移(有=0/无=1) 1.44 0.86~2.42 0.171
    下载: 导出CSV

    表  5  OS的多变量Cox比例风险模型分析

    Table  5.   Multivariable Cox proportional hazards model for overall survival

    变量 HR 95%CI P
    ORR(是=0/否=1) 0.20 0.09~0.43 <0.001
    肿瘤最大径(≤7 cm=0/>7 cm=1) 0.45 0.21~0.99 0.048
    AFP(≥400 ng/mL=0/<400 ng/mL=1) 1.06 0.57~1.97 0.874
    Child-Pugh分级(7分=0/8~9分=1) 1.29 0.72~2.31 0.403
    下载: 导出CSV
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  • 收稿日期:  2023-09-19
  • 录用日期:  2023-10-18
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